TY  - JOUR
AU  - Biddinger, J.E.
AU  - Elson, A.E.T.
AU  - Fathi, P.A.
AU  - Sweet, S.R.
AU  - Nishimori, K.
AU  - Ayala, J.E.
AU  - Simerly, R.B.
TI  - AgRP neurons mediate activity-dependent development of oxytocin connectivity and autonomic regulation
JF  - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
J2  - P NATL ACAD SCI USA
VL  - 121
PY  - 2024
IS  - 49
SN  - 0027-8424
DO  - 10.1073/pnas.2403810121
UR  - https://m2.mtmt.hu/api/publication/35682062
ID  - 35682062
N1  - Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, TN 37232, United States            
            Developmental Neuroscience Program, The Saban Research Institute, Children’s Hospital Los Angeles, Los Angeles, CA 90027, United States            
            Department of Obesity and Internal Inflammation, Fukushima Medical University, Fukushima City, 960-1295, Japan            
            Export Date: 13 January 2025            
            CODEN: PNASA            
            Correspondence Address: Simerly, R.B.; Department of Molecular Physiology & Biophysics, United States; email: richard.simerly@vanderbilt.edu            
            Chemicals/CAS: clozapine, 5786-21-0; corticotropin releasing factor, 9015-71-8, 178359-01-8, 79804-71-0, 86297-72-5, 86784-80-7; oxytocin, 50-56-6, 54577-94-5; Agouti-Related Protein; Agrp protein, mouse; Leptin; Oxytocin; Receptors, Leptin            
            Tradenames: GraphPad Prism software Version 9.5            
            Funding details: National Institutes of Health, NIH, DK106476            
            Funding details: National Institutes of Health, NIH            
            Funding text 1: ACKNOWLEDGMENTS.This work was supported by NIH grant DK106476 to R.B.S. We would like to thank Jessie Zimmermann and Nicholas Thomas-Low for excellent histochemical support.We would also like to thank Dollada Srisai for providing technical assistance,Dong Zhou and Frohar Mirzai for animal care,as well as all members of the Simerly Lab for helpful discussion and input on the manuscript.We appreciate thegenerosity of LarryYoung (Emory University)forproviding breeders to establish a local colony of Oxytocin-Receptor-Venus mice and for the expert assistance of the Mouse Metabolic Phenotyping Core at Vanderbilt University.
AB  - During postnatal life, leptin specifies neuronal inputs to the paraventricular nucleus of the hypothalamus (PVH) and activates agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus. Activity-dependent developmental mechanisms impact refinement of sensory circuits, but whether leptin-mediated postnatal neuronal activity specifies hypothalamic neural projections is largely unexplored. Here, we used chemogenetics to manipulate the activity of AgRP neurons during a discrete postnatal critical period and evaluated the development of AgRP inputs to the PVH and descending efferent outflow to the dorsal vagal complex (DVC). In leptin-deficient mice, targeting of AgRP neuronal outgrowth to PVH oxytocin neurons was reduced, and despite the lack of leptin receptors found on oxytocin neurons in the PVH, oxytocin-containing connections to the DVC were also impaired. Activation of AgRP neurons during early postnatal life not only normalized AgRP inputs to the PVH but also oxytocin outputs to the DVC in leptin-deficient mice. Blocking AgRP neuron activity during the same postnatal period reduced the density of AgRP inputs to the PVH of wild type mice, as well as the density of oxytocin-containing DVC fibers, and these innervation deficits were associated with dysregulated autonomic function. These findings suggest that leptin-mediated AgRP neuronal activity is required for the development of PVH connectivity and represents a unique activity-dependent mechanism for specification of neural pathways involved in the hypothalamic integration of autonomic responses. Copyright © 2024 the Author(s).
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Cai, J.
AU  - Jiang, Y.
AU  - Xu, Y.
AU  - Jiang, Z.
AU  - Young, C.
AU  - Li, H.
AU  - Ortiz-Guzman, J.
AU  - Zhuo, Y.
AU  - Li, Y.
AU  - Xu, Y.
AU  - Arenkiel, B.R.
AU  - Tong, Q.
TI  - An excitatory projection from the basal forebrain to the ventral tegmental area that underlies anorexia-like phenotypes
JF  - NEURON
J2  - NEURON
VL  - 112
PY  - 2024
IS  - 3
SP  - 458
EP  - 472.e6
SN  - 0896-6273
DO  - 10.1016/j.neuron.2023.11.001
UR  - https://m2.mtmt.hu/api/publication/34580658
ID  - 34580658
N1  - Brown Foundation of Molecular Medicine for the Prevention of Human Diseases of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, United States            
            MD Anderson Cancer Center & UTHealth Graduate School for Biomedical Sciences, University of Texas Health Science at Houston, Houston, TX 77030, United States            
            Department of Molecular and Human Genetics and Department of Neuroscience, Baylor College of Medicine, and Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, United States            
            State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Beijing, 100871, China            
            USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, United States            
            Department of Neurobiology and Anatomy of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, United States            
            Export Date: 14 February 2024            
            CODEN: NERNE            
            Correspondence Address: Arenkiel, B.R.; Department of Molecular and Human Genetics and Department of Neuroscience, United States; email: arenkiel@bcm.edu            
            Correspondence Address: Tong, Q.; Brown Foundation of Molecular Medicine for the Prevention of Human Diseases of McGovern Medical School, United States; email: qingchun.tong@uth.tmc.edu            
            Chemicals/CAS: dopamine, 51-61-6, 62-31-7            
            Funding details: National Institutes of Health, NIH, R01 DK120858, R01 DK135212, R01DK109934, R01DK131446, R01DK136284            
            Funding details: U.S. Department of Defense, DOD, HT94252310156            
            Funding details: Russell and Diana Hawkins Family Foundation            
            Funding details: McGovern Medical School            
            Funding text 1: We acknowledge Dr. Yulong Li for providing the gDA3m vector. This study was supported by the NIH R01 DK135212, R01DK131446, and R01DK136284 (Q.T.); R01 DK120858 (Q.T. and Yong Xu); R01DK109934 and DOD HT94252310156 (Q.T. and B.R.A.). Q.T. is the holder of the Cullen Chair in Molecular Medicine at McGovern Medical School. J.C. is the awardee of the Russell and Diana Hawkins Family Foundation Discovery Fellowship. The figure abstract and some diagrams were created with BioRender.com. J.C. conducted the major part of research with help from Y.J. Yuanzhong Xu, and Z.J. Y.J. conducted the brain-slice recordings. J.O.-G. B.R.A. Yong Xu, Y.Z. and Y.L. provided essential reagents. Q.T. and B.R.A. conceived and designed the experiments and wrote the manuscript with significant inputs from all authors. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research.            
            Funding text 2: We acknowledge Dr. Yulong Li for providing the gDA3m vector. This study was supported by the NIH R01 DK135212 , R01DK131446 , and R01DK136284 (Q.T.); R01 DK120858 (Q.T. and Yong Xu); R01DK109934 and DOD HT94252310156 (Q.T. and B.R.A.). Q.T. is the holder of the Cullen Chair in Molecular Medicine at McGovern Medical School. J.C. is the awardee of the Russell and Diana Hawkins Family Foundation Discovery Fellowship. The figure abstract and some diagrams were created with BioRender.com .
AB  - Maladaptation in balancing internal energy needs and external threat cues may result in eating disorders. However, brain mechanisms underlying such maladaptations remain elusive. Here, we identified that the basal forebrain (BF) sends glutamatergic projections to glutamatergic neurons in the ventral tegmental area (VTA) in mice. Glutamatergic neurons in both regions displayed correlated responses to various stressors. Notably, in vivo manipulation of BF terminals in the VTA revealed that the glutamatergic BF → VTA circuit reduces appetite, increases locomotion, and elicits avoidance. Consistently, activation of VTA glutamatergic neurons reduced body weight, blunted food motivation, and caused hyperactivity with behavioral signs of anxiety, all hallmarks of typical anorexia symptoms. Importantly, activation of BF glutamatergic terminals in the VTA reduced dopamine release in the nucleus accumbens. Collectively, our results point to overactivation of the glutamatergic BF → VTA circuit as a potential cause of anorexia-like phenotypes involving reduced dopamine release. © 2023 Elsevier Inc.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - D'ávila, M.
AU  - Hall, S.
AU  - Horvath, T.L.
TI  - GLP-1, GIP, and Glucagon Agonists for Obesity Treatment: A Hunger Perspective
JF  - ENDOCRINOLOGY
J2  - ENDOCRINOLOGY
VL  - 165
PY  - 2024
IS  - 11
SN  - 0013-7227
DO  - 10.1210/endocr/bqae128
UR  - https://m2.mtmt.hu/api/publication/35616600
ID  - 35616600
N1  - Department of Comparative Medicine, Yale School of Medicine, New Haven, CT 06520, United States            
            Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06520, United States            
            Export Date: 2 December 2024            
            CODEN: ENDOA            
            Correspondence Address: Horvath, T.L.; Department of Comparative Medicine, 310 Cedar Street, United States; email: tamas.horvath@yale.edu
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Price, N.L.
AU  - Fernández-Tussy, P.
AU  - Varela, L.
AU  - Cardelo, M.P.
AU  - Shanabrough, M.
AU  - Aryal, B.
AU  - de, Cabo R.
AU  - Suárez, Y.
AU  - Horváth, Tamás
AU  - Fernández-Hernando, C.
TI  - microRNA-33 controls hunger signaling in hypothalamic AgRP neurons
JF  - NATURE COMMUNICATIONS
J2  - NAT COMMUN
VL  - 15
PY  - 2024
IS  - 1
SN  - 2041-1723
DO  - 10.1038/s41467-024-46427-0
UR  - https://m2.mtmt.hu/api/publication/34766210
ID  - 34766210
N1  - Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, United States            
            Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, United States            
            Yale Center for Molecular and System Metabolism. Yale University School of Medicine, New Haven, CT, United States            
            Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, United States            
            Laboratory of Glia -Neuron Interactions in the control of Hunger. Achucarro Basque Center for Neuroscience, Vizcaya, Leioa, 48940, Spain            
            IKERBASQUE, Basque Foundation for Science, Vizcaya, Bilbao, 48009, Spain            
            Department of Pathology. Yale University School of Medicine, New Haven, CT, United States            
            Department of Neuroscience. Yale University School of Medicine, New Haven, CT, United States            
            Export Date: 3 April 2024            
            Correspondence Address: Fernández-Hernando, C.; Vascular Biology and Therapeutics Program, United States; email: carlos.fernandez@yale.edu            
            Correspondence Address: Horvath, T.L.; Department of Comparative Medicine, United States; email: tamas.horvath@yale.edu            
            Chemicals/CAS: Agouti-Related Protein; MicroRNAs; Mirn33 microRNA, mouse            
            Funding details: National Institutes of Health, NIH, 1K01DK120794, AG067329, DA046160, DK045735, DK120891, DK126447, R35HL135820, R35HL155988            
            Funding details: American Heart Association, AHA, 20TPA35490416, 23CDA1055007, 874771            
            Funding details: Klarman Family Foundation, KFF            
            Funding details: Ministerio de Ciencia e Innovación, MCIN            
            Funding details: Agencia Estatal de Investigación, AEI, PID2021-125193OA-I00            
            Funding text 1: This work was at least in part supported by grants from the National Institutes of Health (R35HL135820 to CF-H; and R35HL155988 to YS; 1K01DK120794 to NP; and DK120891, DA046160, DK045735, AG067329 and DK126447 to TLH), the American Heart Association (20TPA35490416 to CF-H; and 874771 and 23CDA1055007 to PF-T), the Klarman Family Foundation to TLH and Plan Generación Conocimiento from the Spanish Ministry of Science and Innovation and Agencia Estatal de Investigación (PID2021-125193OA-I00 to LV). Schemes in Figs. , and and Supplementary Figs. 2a and d and 3a and f were generated using BioRender.com.
AB  - AgRP neurons drive hunger, and excessive nutrient intake is the primary driver of obesity and associated metabolic disorders. While many factors impacting central regulation of feeding behavior have been established, the role of microRNAs in this process is poorly understood. Utilizing unique mouse models, we demonstrate that miR-33 plays a critical role in the regulation of AgRP neurons, and that loss of miR-33 leads to increased feeding, obesity, and metabolic dysfunction in mice. These effects include the regulation of multiple miR-33 target genes involved in mitochondrial biogenesis and fatty acid metabolism. Our findings elucidate a key regulatory pathway regulated by a non-coding RNA that impacts hunger by controlling multiple bioenergetic processes associated with the activation of AgRP neurons, providing alternative therapeutic approaches to modulate feeding behavior and associated metabolic diseases. © The Author(s) 2024.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Sayar-Atasoy, N.
AU  - Yavuz, Y.
AU  - Laule, C.
AU  - Dong, C.
AU  - Kim, H.
AU  - Rysted, J.
AU  - Flippo, K.
AU  - Davis, D.
AU  - Aklan, I.
AU  - Yilmaz, B.
AU  - Tian, L.
AU  - Atasoy, D.
TI  - Opioidergic signaling contributes to food-mediated suppression of AgRP neurons
JF  - CELL REPORTS
J2  - CELL REP
VL  - 43
PY  - 2024
IS  - 1
SN  - 2639-1856
DO  - 10.1016/j.celrep.2023.113630
UR  - https://m2.mtmt.hu/api/publication/34506563
ID  - 34506563
N1  - Department, of Neuroscience and Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States            
            Department of Physiology, School of Medicine, Yeditepe University, Istanbul, 34755, Turkey            
            Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, Davis, CA 95616, United States            
            Iowa Neuroscience Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States            
            Fraternal Order of Eagles Diabetes Research Center (FOEDRC), Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States            
            Export Date: 16 January 2024            
            Correspondence Address: Atasoy, D.; Department, United States; email: deniz-atasoy@uiowa.edu            
            Chemicals/CAS: opiate, 53663-61-9, 8002-76-4, 8008-60-4
AB  - Opioids are generally known to promote hedonic food consumption. Although much of the existing evidence is primarily based on studies of the mesolimbic pathway, endogenous opioids and their receptors are widely expressed in hypothalamic appetite circuits as well; however, their role in homeostatic feeding remains unclear. Using a fluorescent opioid sensor, deltaLight, here we report that mediobasal hypothalamic opioid levels increase by feeding, which directly and indirectly inhibits agouti-related protein (AgRP)-expressing neurons through the μ-opioid receptor (MOR). AgRP-specific MOR expression increases by energy surfeit and contributes to opioid-induced suppression of appetite. Conversely, its antagonists diminish suppression of AgRP neuron activity by food and satiety hormones. Mice with AgRP neuron-specific ablation of MOR expression have increased fat preference without increased motivation. These results suggest that post-ingestion release of endogenous opioids contributes to AgRP neuron inhibition to shape food choice through MOR signaling. © 2023 The Author(s)
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Wu, S.
AU  - Wang, J.
AU  - Zhang, Z.
AU  - Jin, X.
AU  - Xu, Y.
AU  - Si, Y.
AU  - Liang, Y.
AU  - Ge, Y.
AU  - Zhan, H.
AU  - peng, L.
AU  - Bi, W.
AU  - Luo, D.
AU  - Li, M.
AU  - Meng, B.
AU  - Guan, Q.
AU  - Zhao, J.
AU  - Gao, L.
AU  - He, Z.
TI  - Shank3 deficiency elicits autistic-like behaviors by activating p38α in hypothalamic AgRP neurons
JF  - MOLECULAR AUTISM
J2  - MOL AUTISM
VL  - 15
PY  - 2024
IS  - 1
SN  - 2040-2392
DO  - 10.1186/s13229-024-00595-4
UR  - https://m2.mtmt.hu/api/publication/34836144
ID  - 34836144
N1  - Department of Endocrinology, Shandong Provincial Hospital & amp; Medical Integration, and Practice Center, Shandong University, Shandong, Jinan, 250021, China            
            Key Laboratory of Endocrine Glucose & amp; Lipids Metabolism and Brain Aging, Ministry of Education, Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Shandong Institute of Endocrine and Metabolic Diseases, Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Shandong Prevention and Control Engineering Laboratory of Endocrine and Metabolic Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, Jinan, 250021, China            
            Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Shandong, Jinan, 250021, China            
            School of Modern Posts, Nanjing University of Posts and Telecommunications, Jiangsu, Nanjing, 210009, China            
            Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Shandong, Jinan, 250012, China            
            Key Laboratory of Brain Functional Genomics, Ministry of Education, School of Life Sciences，East China Normal University, Shanghai, 200062, China            
            Department of Pharmacology and Chemical Biology, Department of Neurology, Emory University, Atlanta, GA 30322, United States            
            Cheeloo College of Medicine, Shandong Provincial Hospital, Shandong University, 544 Jingsi Road, Shandong, Jinan, 250021, China            
            Export Date: 6 May 2024            
            Correspondence Address: He, Z.; Department of Endocrinology, Shandong, China; email: zhaohe@sdu.edu.cn            
            Chemicals/CAS: mitogen activated protein kinase 1, 137632-08-7; mitogen activated protein kinase 3, 137632-07-6; proopiomelanocortin, 66796-54-1; stress activated protein kinase, 155215-87-5; Agouti-Related Protein; Microfilament Proteins; Nerve Tissue Proteins; Shank3 protein, mouse
AB  - Background: SH3 and multiple ankyrin repeat domains protein 3 (SHANK3) monogenic mutations or deficiency leads to excessive stereotypic behavior and impaired sociability, which frequently occur in autism cases. To date, the underlying mechanisms by which Shank3 mutation or deletion causes autism and the part of the brain in which Shank3 mutation leads to the autistic phenotypes are understudied. The hypothalamus is associated with stereotypic behavior and sociability. p38α, a mediator of inflammatory responses in the brain, has been postulated as a potential gene for certain cases of autism occurrence. However, it is unclear whether hypothalamus and p38α are involved in the development of autism caused by Shank3 mutations or deficiency. Methods: Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and immunoblotting were used to assess alternated signaling pathways in the hypothalamus of Shank3 knockout (Shank3−/−) mice. Home-Cage real-time monitoring test was performed to record stereotypic behavior and three-chamber test was used to monitor the sociability of mice. Adeno-associated viruses 9 (AAV9) were used to express p38α in the arcuate nucleus (ARC) or agouti-related peptide (AgRP) neurons. D176A and F327S mutations expressed constitutively active p38α. T180A and Y182F mutations expressed inactive p38α. Results: We found that Shank3 controls stereotypic behavior and sociability by regulating p38α activity in AgRP neurons. Phosphorylated p38 level in hypothalamus is significantly enhanced in Shank3−/− mice. Consistently, overexpression of p38α in ARC or AgRP neurons elicits excessive stereotypic behavior and impairs sociability in wild-type (WT) mice. Notably, activated p38α in AgRP neurons increases stereotypic behavior and impairs sociability. Conversely, inactivated p38α in AgRP neurons significantly ameliorates autistic behaviors of Shank3−/− mice. In contrast, activated p38α in pro-opiomelanocortin (POMC) neurons does not affect stereotypic behavior and sociability in mice. Limitations: We demonstrated that SHANK3 regulates the phosphorylated p38 level in the hypothalamus and inactivated p38α in AgRP neurons significantly ameliorates autistic behaviors of Shank3−/− mice. However, we did not clarify the biochemical mechanism of SHANK3 inhibiting p38α in AgRP neurons. Conclusions: These results demonstrate that the Shank3 deficiency caused autistic-like behaviors by activating p38α signaling in AgRP neurons, suggesting that p38α signaling in AgRP neurons is a potential therapeutic target for Shank3 mutant-related autism. © The Author(s) 2024.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Alpár, Alán
AU  - Verkhratsky, A.
TI  - Mapping the brain in the twenty-first century: Extrahypothalamic projections of TRH neurones
JF  - ACTA PHYSIOLOGICA
J2  - ACTA PHYSIOL
VL  - 238
PY  - 2023
IS  - 3
PG  - 3
SN  - 1748-1708
DO  - 10.1111/apha.14000
UR  - https://m2.mtmt.hu/api/publication/34023969
ID  - 34023969
N1  - Export Date: 2 August 2023            
            Correspondence Address: Verkhratsky, A.; The University of ManchesterUnited Kingdom; email: alexej.verkhratsky@manchester.ac.uk            
            Chemicals/CAS: protirelin, 24305-27-9
LA  - English
DB  - MTMT
ER  -